Effects of sleep-disordered breathing on cerebrovascular regulation: A population-based study.

Rationale: Cerebrovascular regulation is impaired in patients with moderate to severe obstructive sleep apnea; however, it is unknown whether this impairment exists in individuals with less severe sleep-disordered breathing.

Objectives: To test the hypothesis that cerebrovascular responses to hypercapnia are attenuated in a nonclinical population-based cohort.

Methods: A rebreathing test that raised end-tidal CO₂ tension by 10 mm Hg was performed during wakefulness in 373 participants of the Wisconsin Sleep Cohort.

Impaired vascular regulation in patients with obstructive sleep apnea: effects of continuous positive airway pressure treatment.

Rationale: Impaired endothelium-dependent vasodilation has been documented in patients with sleep apnea. This impairment may result in blood flow dysregulation during apnea-induced fluctuations in arterial blood gases.

Objectives: To test the hypothesis that hypoxic and hypercapnic vasodilation in the forearm and cerebral circulation are impaired in patients with sleep apnea.

Resident self-assessment and self-reflection: University of Wisconsin-Madison's Five-Year Study.

Background: Chart review represents a critical cornerstone for practice-based learning and improvement in our internal medicine residency program.

Objective: To document residents' performance monitoring and improvement skills in their continuity clinics, their satisfaction with practice-based learning and improvement, and their ability to self-reflect on their performance.

Design: Retrospective longitudinal design with repeated measures.

Retromandibular fossa approach to the high cervical internal carotid artery: an anatomic study.

Objective: Access to the high cervical internal carotid artery (ICA) is technically challenging for the treatment of lesions in and around this region. The aims of this study were to analyze the efficacy of approaching the high cervical ICA through the retromandibular fossa and to compare preauricular and postauricular incisions. In addition, the relevant neural and vascular structures of this region are demonstrated in cadaveric dissections.

Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia.

Patients with X-linked hypophosphatemia (XLH) and the hyp-mouse, a model of XLH characterized by a deletion in the Phex gene, manifest hypophosphatemia, renal phosphate wasting, and rickets/osteomalacia. Cloning of the PHEX/Phex gene and mutations in affected patients and hyp-mice established that alterations in PHEX/Phex expression underlie XLH. Although PHEX/Phex expression occurs primarily in osteoblast lineage cells, transgenic Phex expression in hyp-mouse osteoblasts fails to rescue the phenotype, suggesting that Phex expression at other sites underlies XLH.

Mechanisms of the cerebrovascular response to apnoea in humans.

We measured ventilation, arterial O2 saturation, end-tidal CO2 (PET,CO2), blood pressure (intra-arterial catheter or photoelectric plethysmograph), and flow velocity in the middle cerebral artery (CFV) (pulsed Doppler ultrasound) in 17 healthy awake subjects while they performed 20 s breath holds under control conditions and during ganglionic blockade (intravenous trimethaphan, 4.4 +/- 1.1 mg min-1 (mean +/- S.

Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a Laboratory Ancillary Study on an Eastern Cooperative Oncology Group Prospective Randomized Trial of Postoperative Adjuvant Therapy.

Purpose: To determine the prognostic and predictive significance of p53 and K-ras mutations in patients with completely resected non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients were randomized preoperatively to receive adjuvant postoperative radiotherapy (Arm A) or radiotherapy plus concurrent chemotherapy (Arm B). p53 protein expression was studied by immunohistochemistry (IHC) and p53 mutations in exons 5 to 8 were evaluated by single-strand conformational analysis.

Potentiation of platinum antitumor effects in human lung tumor xenografts by the angiogenesis inhibitor squalamine: effects on tumor neovascularization.

Squalamine is a novel anti-angiogenic aminosterol that is postulated to inhibit neovascularization by selectively inhibiting the sodium-hydrogen antiporter exchanger. To determine how to most effectively use this agent in patients with cancer, we examined the antitumor effects of squalamine with or without cytotoxic agents in human lung cancer xenografts and correlated these observations with the degree of tumor neovascularization. No direct cytotoxic effects of squalamine against tumor cells were observed in vitro with or without cisplatin.

NMDA-dependent currents in granule cells of the dentate gyrus contribute to induction but not permanence of kindling.

Single-electrode voltage-clamp techniques and bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) were used to study the time course of seizure-induced alterations in NMDA-dependent synaptic currents in granule cells of the dentate gyrus in hippocampal slices from kindled and normal rats. In agreement with previous studies, granule cells from kindled rats examined within 1 wk after the last of 3 or 30-35 generalized tonic-clonic (class V) seizures demonstrated an increase in the NMDA receptor-dependent component of the perforant path-evoked synaptic current. Within 1 wk of the last kindled seizure, NMDA-dependent charge transfer underlying the perforant path-evoked current was increased by 63-111% at a holding potential of -30 mV.

Prolonged depletion of guanosine triphosphate induces death of insulin-secreting cells by apoptosis.

Inhibitors of IMP dehydrogenase, such as mycophenolic acid (MPA) and mizoribine, which deplete cellular GTP, are used clinically as immunosuppressive drugs. The prolonged effect of such agents on insulin-secreting beta-cells (HIT-T15 and INS-1) was investigated. Both MPA and mizoribine inhibited mitogenesis, as reflected by [3H]thymidine incorporation.

Inhibition of calcium-induced insulin secretion from intact HIT-T15 or INS-1 beta cells by GTP depletion.

Using intact rat islets, we previously observed that GTP depletion (achieved through the use of mycophenolic acid or other synthesis inhibitors) impedes nutrient- but not K+-induced insulin secretion. It was concluded that a proximal nutrient-dependent step in stimulus-secretion coupling (but not the process of Ca2+-induced exocytosis itself) is modulated by ambient GTP levels. To examine Ca2+-dependent steps further in intact beta cells, INS-1 cells (which synthesize GTP and ATP similarly to rat islets) and HIT-T15 cells (whose synthesis of purine nucleotides is different) were studied following cell culture for 1-18 hr in various concentrations of mycophenolic acid (MPA) or mizoribine (MZ).

Roles of GTP and phospholipase C in the potentiation of Ca(2+)-induced insulin secretion by glucose in rat pancreatic islets.

Glucose can augment insulin secretion independently of K+ channel closure, provided cytoplasmic free Ca2+ concentration is elevated. A role for phospholipase C (PLC) in this phenomenon has been both claimed and refuted. Recently, we have shown a role for GTP in the secretory effect of glucose as well as in glucose-induced PLC activation, using islets pre-treated with GTP synthesis inhibitors such as mycophenolic acid (MPA).

Dual functional effects of interleukin-1beta on purine nucleotides and insulin secretion in rat islets and INS-1 cells.

Interleukin-1beta (IL-1beta) has been shown to inhibit glucose-induced insulin secretion from rat islets and purified beta-cells, primarily through the generation of nitric oxide (NO). However, the mechanisms by which NO exerts its effects remain unclear. To examine the role of purine nucleotides, we cultured intact rat islets or INS-1 (glucose-responsive transformed rat) beta-cells for 18 h in the presence or absence of IL-1beta.

Loss of the tumorigenic phenotype with in vitro, but not in vivo, passaging of a novel series of human bronchial epithelial cell lines: possible role of an alpha 5/beta 1-integrin-fibronectin interaction.

We established an immortalized, nontumorigenic human bronchial epithelial cell line by transfection with the origin of replication-defective SV40 large T plasmid. This line spontaneously became tumorigenic at passage 184 (NL20T), although subsequent passages (passages 189, 200, and 205) failed to form tumors. The tumorigenic cell line NL20T was reinoculated back into athymic nude mice, and the two subsequently derived cell lines (NL20T-A and NL20T-B) have been passaged 85 times in vitro and remain tumorigenic.

A comparison of the effects of isoproterenol and forskolin on immunologic and nonimmunologic release of histamine from guinea-pig superfused trachea and dispersed tracheal cells.

This study has compared the abilities of isoproterenol and forskolin to inhibit immunologic- and nonimmunologic-induced histamine release from guinea-pig superfused trachea and enzymatically dispersed tracheal cells. Contraction was also measured in the former preparation. The potency of isoproterenol was similar for inhibition of all parameters associated with immunologic (ovalbumin) challenge in the two preparations.

Measures of body size and growth in rhesus and squirrel monkeys subjected to long-term dietary restriction.

Although many studies have reported the robust effects of dietary restriction (DR) in retarding numerous aging processes in rodents, little is known about the outcomes of reducing caloric intake of a nutritious diet on aging in primates. Most primate studies have concerned the effects of malnutrition. We hypothesized that DR influences aging processes in primate species as it does in rodents.

Technetium 94m-labeled methoxyisobutyl isonitrile: dosimetry and resting cardiac imaging with positron emission tomography.

Background: Development of a positron-emitting form of technetium has allowed the imaging of technetium radiopharmaceuticals with positron emission tomography (PET). We used 94mTc to compare the distribution of the myocardial perfusion agent sestamibi at rest with the conventional PET perfusion tracer 13N-labeled ammonia (13N-ammonia).

Methods And Results: Dosimetry calculations were performed with the known whole-body distribution of 99mTc-labeled sestamibi.

Swallowing after unilateral stroke of the cerebral cortex.

We report differential patterns of swallowing in 40 patients with their first ischemic middle cerebral artery (MCA) stroke and compare these to 20 nonstroke controls. Stroke patients were divided a priori, into groups by right or left and, post hoc, primarily anterior or posterior MCA territory lesions. The left hemisphere subgroup was differentiated from controls by longer pharyngeal transit durations and from the right hemisphere group by shorter pharyngeal response durations.

Diagonal earlobe creases and ischemic stroke: Preliminary report.

Diagonal earlobe creases are associated with coronary arterial disease, cardiac morbidity and mortality, and all-cause mortality. We studied the influence of earlobe creases on the incidence of ischemic stroke as well as the relationship between earlobe creases and gender, coronary arterial disease, hypertension, diabetes mellirus, and hypercholesterolemia. Data were obtained prospectively from the medical records of 116 patients with ischemic stroke and 232 age- and gender-matched patients without ischemic stroke.

Tumor necrosis factor, but not other hematopoietic growth factors, prolongs the survival of hairy cell leukemia cells.

In order to determine the growth factor requirements of hairy cell leukemia (HCL) cells, we studied the in vitro effects of tumor necrosis factor (TNF), interleukin (IL) 1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, B-cell growth factor (BCGF), GM-CSF, PHA-stimulated lymphocyte-conditioned media (CM), and 5637 bladder carcinoma CM on HCL cells obtained from spleens of patients with HCL. Mononuclear cells from a normal donor, obtained at post-traumatic splenectomy, served as a control. TNF prolonged the survival of HCL cells obtained from five different HCL patients when compared to cells cultured in control media alone, although cell proliferation could be demonstrated in only two of the five.

Immunological effects of levamisole in vitro.

Levamisole, an anthelminthic drug with immunological properties, has recently been reported to have antitumor activity when administered with 5-fluorouracil in patients with Duke's C colorectal carcinoma. The mechanism of this antitumor effect is unknown, but has been postulated to be related to levamisole's immunomodulatory properties. To define further the immunomodulatory activities of levamisole, we studied the in vitro effects of levamisole on monocyte and lymphocyte cytotoxicity, activation, and proliferation; induction of cytokine-induced proteins; and expression of tumor-associated antigens.

Establishment and characterization of an Epstein-Barr virus spontaneously transformed lymphocytic cell line derived from a hairy cell leukemia patient.

Hairy cell leukemia is a rare, B-cell malignancy uniquely sensitive to the antitumor effects of alpha and beta interferons (IFN). In order to further study the effects of IFN in this disease, we derived a cell line (HC1) from the peripheral blood mononuclear cells of a patient with hairy cell leukemia (HCL). Cells exhibited the typical morphological features of HCL, including the characteristic cytoplasmic projections by light, transmission, and scanning electron microscopy.

Allergens involved in occupational asthma caused by baby's breath (Gypsophila paniculata).

Although the floral industry deals with many potential allergens, few examples of occupational asthma exist in this industry. A 22-year-old florist experienced symptoms of rhinitis, conjunctivitis, and asthma on exposure to baby's breath. To determine the contribution of baby's breath to the patient's symptoms, an extract of baby's breath was prepared.

Occupational sensitivity to Tenebrio molitor Linnaeus (yellow mealworm).

Tenebrio molitor is an abundant stored-grain pest in the northern United States. We evaluated an individual with work-related symptoms of rhinoconjunctivitis on exposure to this insect. Prick skin tests with extracts prepared from the larval, pupal, and adult-life stages were positive for the patient and for another individual with allergy to a closely related species of beetle, Alphitobius diaperinus.

Characterization of the synergistic antiproliferative effects of interferon-gamma and tumor necrosis factor on human colon carcinoma cell lines.

We employed a tumor-type-specific tissue culture model utilizing three human colon carcinoma cell lines to (i) assess the effects of schedule, sequence, dose, and duration of exposure on the antiproliferative activity of combinations of tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) and to (ii) determine the effects of this combination on the production of a TNF-inducible protein, IFN-beta 2, and an IFN-inducible protein, p78. A statistical model was developed to ascertain the effects of each of three of the variables (sequence, dose, and duration) on the other two. With minor exceptions, the maximal antiproliferative effect in all three cell lines was observed when IFN-gamma and TNF were administered simultaneously, regardless of the doses of each agent and duration of exposure.